Mitotane (o,p′-DDD or 1,1-dichlorodiphenyldichloroethane) is an adrenolytic agent which is particularly useful in the treatment of non-resectable and metastasized adrenocortical carcinoma.
However mitotane has poor solubility in gastro-intestinal tract and low bioavailability when administered as a conventional tablet in humans. Attempts were made to solve this problem. A first self-microemulsifying drug delivery system (“SMEDDS”) of mitotane was developed, comprising mitotane dissolved in a matrix composed of an equal mixture of Capryol®90, Tween®20 and Cremophor EL® (33:33:33) (Attivi et al, “Development of a self-microemulsifying drug delivery system of mitotane (o,p′-DDD) using a mixture design methodology”, Chimiometrie 2006, Ajana Imane, 2006, Master “Sciences de la vie et de la santé”, Nancy-Université). However this system could not load more than 250 mg of mitotane in 1000 mg of matrix, which is not enough to produce capsules of an acceptable size and would therefore seriously entail patients' compliance with the treatment. Optimization of this system was thus needed.